MicroRNA-1296-5p suppresses the proliferation, migration, and invasion of human osteosarcoma cells by targeting NOTCH2.

Osteosarcoma (OS) is a highly aggressive bone tumor with a poor prognosis. MicroRNAs are revealed to exerts essential roles in the carcinogenesis and tumor invasion of OS. But, the function of miR-1296-5p and its related mechanism in OS progression have not yet been studied. This study discovered the levels of miR-1296-5p in OS and corresponding noncancerous tissues, and we demonstrated that miR-1296-5p level was markedly downregulated in tumor specimens as compared with nontumor tissues. In addition, we discovered that miR-1296-5p was also underexpressed in OS cells compared with the hFOB1.19 osteoblast cells. Interestingly, the reduced expression of miR-1296-5p was confirmed to associated with large tumor size, advanced tumor stages, and distance metastasis, respectively. Patients with OS low-expressing miR-1296-5p showed a prominent shorter survival. In addition, gain-of-function assays verified that miR-1296-5p overexpression remarkably repressed OS cell proliferation, migration, and invasion. Conversely, depletion of miR-1296-5p facilitated the growth and mobility of OS cells. Notably, miR-1296-5p inversely modulated notch receptor 2 (NOTCH2) in OS cells. The level of NOTCH2 messenger RNA was negatively correlated with miR-1296-5p level in OS samples. NOTCH2 knockdown markedly suppressed the abilities of MG-63 cell proliferation and mobility. More importantly, the restoration of NOTCH2 prominently rescued miR-1296-5p-induced tumor-suppressive effects on MG-63 cells. In conclusion, our study identified the reduced expression of miR-1296-5p, which contributed to OS progression. miR-1296-5p might be a promising prognostic marker and therapeutic target in OS.

Wang L ，Hu K ，Chao Y ，Wang X ... -  《-》

Increased Expression of microRNA-199b-5p Associates with Poor Prognosis Through Promoting Cell Proliferation, Invasion and Migration Abilities of Human Osteosarcoma.

Zeng H ，Zhang Z ，Dai X ，Chen Y ，Ye J ，Jin Z ... -  《-》

Long non-coding RNA XIST promotes osteosarcoma progression by targeting YAP via miR-195-5p.

The lncRNA XIST (X inactive-specific transcript) is an oncogenic lncRNA that is present in various malignant tumors; however, its role and molecular mechanisms in osteosarcoma (OS) progression remain unclear. In the current study, 40 pairs of OS tissues and matched adjacent non-tumor tissues were collected. qRT-PCR was conducted to investigate the differences in XIST expression in tissues and OS cell lines. The proliferation, invasion, and EMT status of OS cells after transfection were assessed with WST-1 assays, Transwell assays, and Western blot analysis, respectively. Whether miR-195-5p was a direct downstream target of XIST was verified by both bioinformatics target gene prediction and dual-luciferase report analysis. A mouse model was established to evaluate tumor proliferation in vivo. Our results demonstrated that XIST expression was significantly upregulated in OS tissues and cell lines and negatively correlated with clinical prognosis. XIST knockdown inhibited cancer cell proliferation and invasion in vitro, inhibited the EMT of OS cells in vitro, and suppressed subcutaneous tumor growth in vivo. Further analysis demonstrated that XIST regulated YAP expression by functioning as a competing endogenous RNA that sponged miR-195-5p in OS cells. XIST directly interacted with miR-195-5p and decreased the binding of miR-195-5p to the YAP 3'UTR, which suppressed the degradation of YAP mRNA by miR-195-5p. In conclusion, this work demonstrates that lncRNA XIST enhances OS cancer cell proliferation and invasion in part through the miR-195-5p/YAP pathway. Therefore, lncRNA XIST might be a promising therapeutic target for OS.

Yang C ，Wu K ，Wang S ，Wei G ... -  《-》

lncRNA nuclear-enriched abundant transcript 1 promotes cell proliferation and invasion by targeting miR-186-5p/HIF-1α in osteosarcoma.

Increasing evidence shows that the long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) plays important roles in tumor progression. However, the function and the underlying mechanism of NEAT1 in osteosarcoma (OS) remain unclear. In the present study, we found that NEAT1 expression was significantly upregulated in OS tissues and cell lines. High NEAT1 expression was closely associated with advanced clinicopathologic features and poor overall survival of patients with OS. Using in vitro function assay, we found that NEAT1 could promote the proliferation, invasion, and epithelial-mesenchymal transition (EMT) process of OS cells. NEAT1 could also promote OS cell growth in vivo. In addition, our studies showed that miR-186-5p was a downstream target of NEAT1 in OS. Functionally, miR-186-5p suppressed the proliferation, invasion, and EMT process of OS cells. Furthermore, our data revealed that HIF-1α was a downstream target of miR-186-5p and that NEAT1 could exert its tumor oncogenic roles on OS cells via the miR-186-5p/HIF-1α axis. Taking our results together, we elucidated that the NEAT1/miR-186-5p/HIF-1α axis might be a therapeutic approach for the treatment of OS.

Tan H ，Zhao L 《-》

LncRNA TMPO-AS1 serves as a ceRNA to promote osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis.

Cui H ，Zhao J 《-》